The same extrachromosomal plasmids in bacteria that determine resistances to many antibiotics also determine resistances to heavy metals, such as mercury, cadmium, lead, arsenic and silver. These resistance plasmids are frequently found in clinical isolates from both gram-negative and gram-positive bacteria. For ten years we have been studying the mechanism of resistances to inorganic Hg2 ion and to organomercurials such as phenylmercury and methylmercury. The mechanism is one of enzymatic detoxification and we have purified and characterized the enzymes involved. Current work includes a comparative immunological approach to the relationships among mercuric reductase enzymes in gram-negative and gram-positive bacteria. We are also continuing the molecular genetic analysis of the operon that governs these resistances. Cadmium resistance is due to a transport alteration involving the interaction between Cd ion and Mn2 ion. We are continuing these studies in subcellular membrane ghosts. Arsenate, arsenite and antimony resistances are governed by an inducible operon structure in both gram-negative and gram-positive bacteria. We have determined that the mechanism of arsenate resistance is a transport alteration affecting the interaction of arsenate and the two bacterial phosphate transport systems. We will continue seeking the mechanisms of arsenite and antimony resistances. Silver resistance plasmids have only been found very recently. We are seeking the mechanism of silver resistance that may be due to specific silver-binding sites on the cell surface and is affected by the binding of Ag ion by the bacterial cell relative to "typing up" of Ag ion in AgCl precipitates and complexes.